Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Zikherman and colleagues uncover a new mechanism by which B cells recognize virus-like antigen display as a stand-alone danger signal (independent of nucleic acid cargo) that does not rely exclusively on avidity and BCR cross-linking.
The DNA-binding domains of transcription factors have been well characterized, but whether their intrinsically disordered regions control cell fate is unclear. Here, the authors show the functional and mechanistic importance of an intrinsically disordered region of TCF-1 in T cell development.
Thomas and colleagues examine preinfection baseline parameters of cellular and serologic immunity. Their findings collectively show that peripheral cell composition provides better correlates of immune protection from symptomatic influenza infection than vaccination, demographics or serology alone.
Here, the authors show that short-term consumption of energy-dense diets deficient in fiber, similar to eating patterns for many people today, results in a transient depression of the mucosal and systemic immune systems such that susceptibility to bacterial infection is increased.
Streets, Yosef, Robey and colleagues use multiomics analysis to generate a comprehensive timeline of the CD4+ and CD8+ T cell lineage commitment and identify sequential waves of TCR signaling that first initiate CD4+ T cell lineage differentiation and then CD8+ T cells lineage specification.
Garner et al. analyzed the single-cell transcriptome and TCR repertoire of matched blood and liver, and resting and activated, human MAIT cells. They identify donor-specific TCR repertoires shared across tissues and a transcriptome that is largely homogeneous at rest, but highly adaptive to different tissue and stimulation environments.
Runx family proteins direct lineage-fate decisions in multiple cell types. Here, Rothenberg and colleagues show how limited Runx protein abundance dictates T cell lineage developmental kinetics through competition for binding by its protein interaction partners.
Here the authors identify genetic effectors of the level of inflammation-related plasma proteins and use Mendelian randomization to identify proteins that contribute to immune-mediated disease risk.
DeNardo and colleagues show that tissue-resident macrophages (TRMs) have a protective role during pancreas inflammation by triggering the activation of fibroblasts, but that TRM-driven fibrosis drives pancreas cancer pathogenesis.
In inflammation, some regulatory T (Treg) cells lose FoxP3 expression and become exTreg cells. Ley and colleagues mapped mouse Treg and exTreg cell transcriptomes to a human peripheral blood mononuclear cell single-cell RNA-sequencing dataset with surface markers (CITE-seq) and identify human exTreg cells as cytotoxic CD4+ T cells.
Rudloff et al. examine the kinetics of CD8+ T cell dysfunction/exhaustion. Tumor-specific CD8+ T cells in the tumor environment exhibit epigenetic modifications within hours, before cell division. The findings suggest a temporal relationship between tumor antigen exposure, chromatin remodeling and dysfunction ‘imprinting’.
Sen et al. provide in-depth temporal multi-omic analyses with single-cell RNA-sequencing (scRNA-seq) profiles of nuclear factor kappa B (NF-κB)-regulated gene expression in B cells upon B cell receptor (BCR) activation. Their findings reveal distinct kinetic patterns of gene expression mediated by RelA and Rel and functional antagonism between the closely related NF-κB subunits.
Chimeric antigen receptor (CAR)-T cells may become exhausted, non-functional or deplete their target cells of antigen, limiting their efficacy. Chen and colleagues fuse the CTLA-4 cytoplasmic tail to a CAR, which compromises trogocytosis and increases the functional capacity of CAR-T cells.
Stevens and colleagues show that human stem-cell-differentiated microglia can be used to model the extensive transcriptional diversity of human brain microglia.
To kill target cells, cytotoxic T lymphocytes (CTLs) form an immune synapse (IS) to elicit cell death and the IS then dissolves to allow for CTL serial killing. Huse et al. find that IS dissolution occurs concomitantly with cytoskeletal contraction of apoptotic targets and this is both necessary and sufficient for CTL dissociation
As the Plasmodium species that cause malaria replicate in the liver, Heath and colleagues designed mRNA vaccines to limit infection by inducing liver-resident memory T cells. Efficacy was observed in mice, including in hosts with previous blood-stage infection.
Basu et al. find that the transcription factor ThPOK is not restricted to T cells, as it also is expressed in myeloid cell progenitors and contributes to the lineage choice of monocyte-dendritic cells as opposed to neutrophils.
Young children frequently encounter respiratory pathogens that elicit immune responses in developing lungs. Farber and colleagues examine rare lung tissue samples obtained from pediatric organ donors and find age-dependent formation of bronchus-associated lymphoid tissue (BALT), which peaks at 3 years of age and dissipates thereafter. Profiling of BALT lymphocytes indicates that repertoire and functional differences exist between the lung, draining lymph nodes and circulating cells.